Emory National Primate Research Center, Emory University, Atlanta, Georgia, United States.
Udall Center of Excellence in Parkinson's Disease Research, Department of Neurology/School of Medicine, Emory University, Atlanta, Georgia, United States.
J Neurophysiol. 2023 May 1;129(5):1010-1020. doi: 10.1152/jn.00265.2022. Epub 2023 Apr 5.
The spiking activity of basal ganglia neurons can be characterized by summary statistics such as the average firing rate, or by measures of firing patterns, such as burst discharges, or oscillatory fluctuations of firing rates. Many of these features are altered by the presence of parkinsonism. This study examined another distinct attribute of firing activity, i.e., the occurrence of repeating sequences of interspike intervals (ISIs). We studied this feature in extracellular electrophysiological recordings that were made in the basal ganglia of rhesus monkeys, before and after they had been rendered parkinsonian by treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurons in both pallidal segments and in the subthalamic nucleus tended to fire in repeating sequences, typically two ISIs long (i.e., involving three spikes). In recordings that were 5,000 interspike intervals long, 20%-40% of spikes participated in one of many sequences with each ISI replicating the sequence pattern with a timing error of ≤1%. Compared with similar analyses in shuffled representations of the same data, sequences were more common in the original representation of ISIs in all of the tested structures. Induction of parkinsonism reduced the proportion of sequence spikes in the external pallidum but increased it in the subthalamic nucleus. We found no relation between the sequence generation and the firing rate of neurons, and, at most, a weak correlation between sequence generation and the incidence of bursts. We conclude that basal ganglia neurons fire in recognizable sequences of ISIs, whose incidence is influenced by the induction of parkinsonism. Previous work has shown that the timing of the electrical activity of basal ganglia neurons has nonstochastic properties, resulting in oscillatory firing patterns, or bursting. This article describes another such property in the monkey brain; a surprisingly large proportion of action potentials generated by cells in the extrastriatal basal ganglia are part of precisely timed recurring sequences of spiking events. We also found that the generation of these sequences changes substantially in the parkinsonian state.
基底神经节神经元的尖峰活动可以用摘要统计数据来描述，例如平均放电率，或者用放电模式的度量来描述，例如爆发放电，或者放电率的振荡波动。这些特征中有许多都因帕金森病的存在而改变。本研究检查了放电活动的另一个独特属性，即尖峰间间隔 (ISI) 的重复序列的发生。我们在恒河猴的基底神经节中进行了细胞外电生理记录，在使用神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶使它们产生帕金森病之前和之后研究了这个特征。苍白球的两个节段和丘脑下核中的神经元往往会以重复的序列放电，通常是两个 ISI 长（即涉及三个尖峰）。在 5000 个尖峰间隔长的记录中，20%-40%的尖峰参与了许多序列中的一个，每个 ISI 复制序列模式的时间误差≤1%。与相同数据的随机表示的类似分析相比，在所有测试结构中，原始 ISI 表示中的序列更为常见。帕金森病的诱导减少了外苍白球中序列尖峰的比例，但增加了丘脑下核中的比例。我们没有发现序列生成与神经元放电率之间的关系，最多只是在序列生成与爆发的发生率之间存在弱相关性。我们得出的结论是，基底神经节神经元以可识别的 ISI 序列放电，其发生率受帕金森病诱导的影响。以前的工作表明，基底神经节神经元的电活动具有非随机特性，导致振荡的放电模式或爆发。本文描述了猴子大脑中的另一个这样的特性；外纹状体基底神经节细胞产生的动作电位中，有相当大的一部分是精确定时的重复尖峰事件序列的一部分。我们还发现，这些序列的产生在帕金森病状态下发生了很大的变化。
